Thermo acoustic tomography (TAT) is a rapidly emerging ultrasound-mediated hybrid imaging modality that promises to have a major impact on diagnostic imaging. TAT combines high ultrasonic resolution and strong microwave contrast in a single hybrid modality. Human brain imaging represents an important imaging application that can benefit tremendously by the development of TAT methods. Existing high-resolution human brain imaging modalities such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) are expensive and employ bulky and generally non-portable imaging equipment. Moreover, X-ray CT employs ionizing radiation and is unsafe for patients who need long time monitoring of brain diseases or injuries. Alternatively, ultrasonography is an established portable pediatric brain imaging modality, but its image quality degrades severely when employed after the closure of the fontanels and therefore is not effective for imaging adults. The development of TAT brain imaging methods would circumvent these limitations and result a powerful new brain imaging modality that would fill an important void left by the available techniques. The major technical challenge in TAT brain imaging is to compensate for the distortion introduced into the TAT measurement data by the skull. The broad objective of this proposal is to make TAT brain imaging a practical, useful, and highly effective brain imaging modality by developing robust image reconstruction methods that can account for skull-induced signal distortion and other physical factors. By use of information regarding the skull morphology and composition obtained from previously acquired adjunct image data, or alternatively from the TAT measurement data themselves, we will develop and investigate robust imaging models for TAT that account for the effects of skull-induced wave front aberrations and other physical factors related to the measurement process. We will develop reconstruction algorithms for obtaining accurate images from incomplete data sets that correspond to clinically useful measurement configurations. The developed methods will be systematically evaluated in computer-simulation and experimental studies. The first in vivo study of human TAT brain imaging will also be conducted. The specific aims of the project are: (1) To develop imaging methodologies that incorporate the effects of skull-induced phase aberrations;(2) To develop image reconstruction algorithms for practical brain imaging scanning configurations;(3) To validate the reconstruction methods for TAT brain imaging in computer-simulation studies;and (4) To assess image quality in phantom and in-vivo studies. PUBLIC HEALTH RELEVANCE: The development of thermo acoustic tomography brain imaging will yield a powerful and effective new modality for monitoring brain conditions such as strokes, tumors, and brain injuries. Its specific advantages over existing high-resolution human brain imaging modalities include 1) relatively low-cost, 2) portability that would permit near real-time imaging studies at bedside or in operating rooms, 3) use of non-ionizing radiation, and 4) measurement of structural and functional brain information that is complementary to that revealed by existing methods.